Organophosphine as an Alkyl Transfer Shuttle for the Direct β-Alkylation of Chalcones Using Alkyl Halides

Abstract

We report an efficient alkyl transfer strategy for the direct β-alkylation of chalcones using commercially available alkyl bromides as alkyl reagents. In this transformation, the ortho-phosphanyl substituent in the chalcones is crucial for controlling their reactivity and selectivity. It also serves as a reliable alkyl transfer shuttle to transform electrophilic alkyl bromides into nucleophilic alkyl species in the form of quaternary phosphonium salts and transfer the alkyl group effectively to the β-position of the chalcones. This alkyl transfer strategy can be further extended to the alkenylation of ortho-phosphanyl benzaldehydes to assemble functionalized polyenes.

(E)-1-(5-(Hydroxymethyl) furan-2-yl)-4,4-dimethylpent-1-en-3-one

“…This step is crucial for electron rearrangement, triggering the formation of a new C-C bond. The resulting intermediate undergoes one or multiple proton transfers, eventually leading to an α, β-unsaturated carbonyl compound through a dehydration reaction [17]. This reaction spontaneously occurs in a water-methanol mixed solvent medium, where water likely aids in deprotonation, and methanol helps stabilize the intermediates and the final product.…”